CTLT-05 PRESERVING COGNITIVE FUNCTION DURING RADIOSURGERY FOR METASTATIC BRAIN DISEASE: RESULTS FROM THE COG-SRS TRIAL

Abstract Stereotactic radiosurgery (SRS) is often the treatment of choice for limited metastatic brain disease. However, SRS with standard treatment planning results in cognitive decline in the majority of patients. Herein, we report cognitive outcomes on the first evidence-based, prospective trial of cognitive-sparing SRS (COG-SRS). This single-institution, phase II trial incorporated high-resolution MRI, diffusion tensor tractography, and automated connectome-based processing to delineate 23 white matter tracts (WMT) and the hippocampi for treatment planning. Dose constraints (single-fraction Dmax: WMT = 12 Gy, HC = 8.4 Gy, with 3- and 5-fraction equivalents) to these WMTs were applied based on prior normal tissue complication probability (NTCP) studies. Neuropsychological testing of memory, language, executive function, attention, and fine motor control as well as quality-of-life (QOL) assessments were conducted before and three months post-SRS. The primary outcome of functional preservation was defined as no significant decline in mean test scores, adjusted for age and sex. A total of 78 patients with 186 metastatic lesions were treated with COG-SRS (median age: 63 years, 63% female). Cognitive-sparing dose constraints were achieved in 71% of cases while maintaining target coverage and plan quality. Local control for brain metastases was 98% at 12 months. No significant decline in cognitive function or QOL was observed from baseline to three months post-SRS (p>0.1 for all tests by paired sample t-testing). Patients whose treatment plans could not meet the WMT dose constraint due to tumor location showed significantly greater declines in memory performance (combined Hopkins Verbal Learning Test-Revised and Wechsler Adult Intelligence Score digit span) than those whose plans met the constraints (p=0.02 by Wilcoxon rank-sum test). Image-guided cognitive-sparing SRS using a connectivity framework preserves cognitive and fine motor function while maintaining QOL. Using standard MRI sequences and automated processing, COG-SRS represents a significant advancement in brain radiosurgery.